Immunotherapy With Antibody Delivery Technology for Brain Cancer (Glioblastoma)
arising from glial cells (brain cells for supporting and nourishing neurons). It has extremely fast progression and a poor survival prognosis of 5-year.
Immune checkpoints (IC) are a normal part of the immune system with the role to prevent an immune response from being so strong that it destroys healthy cells in the body. Professor Tasuku Honjo of Kyoto University was also awarded the Nobel Prize in Physiology or Medicine in 2018 for this discovery.
Antibody Delivery Technology
However, these ICIs haven’t proven effective against a variety of cancers including brain metastases, predominantly due to a blood-tumor barrier that suppresses ICIs accumulation in brain tumors, eventually leading to life-threatening immune-related adverse events..
The study thereby developed a technology to potently increase the accumulation of ICIs in brain tumors, and to achieve both therapeutic efficacy and safety.
The team validated results in orthotopic glioblastoma models, where a single administration of the modified Avelumab at 15% (a low dose of 1.5 mg/kg) tallied to 60% complete response rate, with long-term immune memory.
Moreover, the technology also suppressed the immune-related adverse events of Avelumab. The amount of ICI accumulated in the brain tumor site was 33 times higher than that in normal brain tissue, indicating high brain tumor selectivity.
Hence, the modified antibodies achieved potent anti-tumor efficacy against the preclinical GBM model. The study thereby highlights that although GBM is a malignant tumor that recurs frequently, these results are expected to apply to the prevention of GBM recurrence.
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